NDLI: Managing recalcitrant hypercholesterolemia in patients on current best standard of care: efficacy and safety of novel pharmacotherapies

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Managing recalcitrant hypercholesterolemia in patients on current best standard of care: efficacy and safety of novel pharmacotherapies

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Managing recalcitrant hypercholesterolemia in patients on current best standard of care: efficacy and safety of novel pharmacotherapies

Content Provider	Taylor & Francis Online
Author	Sahebkar, Amirhossein Watts, Gerald F.
Abstract	Residual cardiovascular risk in patients with familial hypercholesterolemia (FH) on high-intensity statin therapy with or without ezetimibe and bile acid sequestrants can potentially be addressed by using agents that can further reduce plasma LDL-cholesterol (LDL-C). Two monoclonal antibodies (mAbs; evolocumab and alirocumab) against PCSK9, an antisense oligonucleotide against ApoB100 mRNA (mipomersen; Kynmaro®) and a synthetic small-molecule inhibitor of MTTP (lomitapide; Juxtapid®) are novel lipid-modifying agents that have been shown in Phase II/III studies in FH patients to lower plasma ApoB and LDL-C with a superior efficiency compared with statin monotherapy. Moreover, these agents can modulate plasma levels of other lipid indices, such as triglycerides, HDL-cholesterol (HDL-C) and lipoprotein(a), that are not substantially affected by statins. The new agents act through increased hepatic clearance of ApoB-containing lipoproteins (PCSK9 mAbs) or reduced assembly and secretion of VLDL (mipomersen and lomitapide). Anacetrapib and evacetrapib are newer inhibitors of CETP and can enhance the catabolism of ApoB, accompanied by marked elevations in plasma HDL-C. Mipomersen has been approved by the US FDA, and lomitapide by both the FDA and EMA, as adjunctive to intensive statin therapy and a fat-modified heart-healthy diet in patients with homozygous FH; their use should be accompanied by a careful monitoring of hepatic function owing to the increased risk of hepatic steatosis. PCSK9 mAbs and newer CETP inhibitors are still under investigation but their use in clinical trials has been reported to be safe and well tolerated.
Starting Page	221
Ending Page	233
Page Count	13
File Format	PDF HTM / HTML
ISSN	17584299 17584302
Journal	Clinical Lipidology
Volume Number	9
Issue Number	2
DOI	10.2217/clp.14.14
Language	English
Publisher	Taylor & Francis
Publisher Date	2017-01-18
Access Restriction	Open
Subject Keyword	Antisense oligonucleotide Cardiovascular disease CETP Cholesteryl ester transfer protein Familial and nonamilial hypercholesterolemia Microsomal triglyceride transfer protein MTTP PCSK9 Proprotein convertase subtilisin/kexin type 9
Content Type	Text
Subject	Endocrinology, Diabetes and Metabolism Cardiology and Cardiovascular Medicine

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